Rare Invasive Fungal Infections: Epidemiology, Diagnosis and Management

Rare yeast and filamentous fungi belonging to hyalohyphomycetes (e.g., Scedosporium, Fusarium), zygomycetes and dematiaceous (e.g., Alternaria, Bipolaris) are implicated in human infections ranging from colonization and localized infections in immunocompetent individuals to fungemias and disseminated diseases in immunocompromised patients and accounting <10 % of all isolated fungal pathogens. The diagnosis of yeast, Fusarium and Scedosporium infections is based on blood cultures and of filamentous fungal infections on histopathology, direct microscopy and culture of infected tissues. The panfungal marker 1,3-b-D glucan test as well as cross reaction with antigen tests for other fungi can be used; whereas, PCR assays have been developed for direct detection of these fungi in blood and in tissues. Amphotericin B is the drug of choice for most rare yeast infections except for Trichosporon infections where voriconazole is used. The management of the other infections includes surgery combined with antifungal therapy mainly with amphotericin B for zygomycetes, voriconazole or amphotericin B for hyalohyphomycetes, and itraconazole or amphotericin B for dematiaceous fungi.     

Epidemiology of sporotrichosis in Latin America

Summary Applying the concept of epidemiological chain, it is successively analyzed: the etiologic agent, Sporothrix schenckii and its natural reservoirs (sources of infection); the different ways that infecting particles may reach man (mechanisms of infection); the susceptible population and the population at risk; the incidence and distribution by sex and age in countries of Latin America; the prevalence of the disease according to clinical cases in dermatological clinics and the variation of incidence rates in some countries with time; the influence of the environment mainly climatic conditions on the geographic distribution of the disease.Finally, according to Mackinnon's hypothesis, the climate could have a determining role on the predominance of a certain clinical form on another in different countries.This paper was presented at the X^th ISHAM Congress, Barcelona, Spain, 1988.     

Combination Therapy for Invasive Fungal Infections

The purpose of this review is to summarize and evaluate relevant literature on combination antifungal therapy for invasive fungal infections (IFIs). Cryptococcal meningitis has the largest body and highest quality in support of combination therapy with amphotericin B and flucytosine. More recent data in treatment of invasive aspergillosis suggest combination therapy with voriconazole and echinocandins may be effective in select patients. Quality studies are needed to define combination therapy in rare mold infections. Multiple strategies have been employed to optimize treatment of the growing incidence of IFIs. With exceptions as noted above, justification for the use of combination antifungal therapy is most often based on uncontrolled and/or underpowered studies, in vitro data, and case reports.     

Invasive Pulmonary Fungal Infections in Cystic Fibrosis

Invasive pulmonary mycosis is after allergic bronchopulmonary aspergillosis (ABPA) a frequent and severe complication of CF lung disease. Among CF caregivers, there is an insecurity when and how to treat infections of the lung parenchyma caused by different fungi in patients with CF. This case series provides a multicenter experience on diagnostic, manifestation, and treatment of non-ABPA cases of pulmonary. Non-ABPA cases of pulmonary mycoses in patients with CF have been collected from the CF Centers in Berlin, Essen, Worms, Frankfurt (Germany), Leeds (UK), and Barcelona (Spain). Non-ABPA was defined as total serum IgE level <500 kU/L. Scedosporium and Lomentospora species seem to be more virulent in patients with CF and have been successfully treated with triple antifungal drug regimens in several cases. Rare fungi including yeasts can have pathogenic potential in CF. In this series, antibiotic treatment failure was the main indicator for the initiation of antifungal treatment. For an early and effective treatment of pulmonary mycoses in CF, the identification of biomarkers and of risk factors beyond antibiotic treatment failure is crucial and urgently needed. Furthermore, treatment efficacy studies are necessary for the different causative agents of these infections.     

Histoplasmosis: Epidemiology in Latin America

Histoplasmosis is a frequent health problem in Latin American countries, but the fact that it is not a reportable disease prevents reliable estimates of its real incidence and impact on public health. Epidemiologic and clinical data remain patchy in general, and in some countries the information available is very limited. Histoplasmosis has a significant public health impact in susceptible populations such as immunosuppressed individuals, in whom the disease is associated with poor outcomes. Limited availability of diagnostic tools in many regions of Latin America is an additional problem, as many patients are already severely ill by the time of the diagnosis. Efforts are therefore necessary to ensure early diagnosis and appropriate treatment, limit the severity of the disease manifestations, and reduce morbidity and mortality. This paper reviews important aspects of the epidemiology of histoplasmosis, the most clinically significant endemic mycosis in Latin America.     

Challenges in the Diagnosis of Invasive Fungal Infections in Immunocompromised Hosts

Purpose of review

The expanding population of immunocompromised patients coupled with the recognition of a growing number of different species of fungi responsible for diseases in such hosts makes the diagnosis of invasive fungal infection (IFI) a challenging task. The recent advances and challenges in the diagnosis of IFI in the setting of immunocompromised hosts are reviewed. The advantages and limitations of histopathology and the role of culture-independent methods, such as those based on the use of nucleic acids applied to fresh and formalin-fixed, paraffin-embedded sections, besides culture- and non-culture-based diagnostic methods, to obtain a timely and correct diagnosis of IFI are highlighted.

Recent findings

The therapeutic implications of identifying the genus and species of the fungus present in the specimen with the molecular diagnostics applied to tissue specimens are reviewed. No method alone is efficient in correctly identifying fungi and it is essential to combine the traditional histochemical staining with molecular methods to achieve a rapid and genus-/species-specific diagnosis of IFI.

Summary

We review the recent findings and challenges in the hystopathologic diagnosis of IFI in the setting of immunocompromised hosts. Non method alone is efficient in correctly identify fungi and pathologists should combine classic staining with molecular methods to achieve a rapid and genus/species fungal diagnosis.

     

Invasive Fungal Infections in the Child with Chronic Granulomatous Disease

Invasive fungal infections (IFI) are a major threat for patients with chronic granulomatous disease (CGD) which is an inherited disorder of NADPH oxidase. The absence of a functional NADPH oxidase complex affects the display of an efficient antimicrobial effect as well as a controlled inflammatory response. Invasive aspergillosis caused by either Aspergillus fumigatus or A. nidulans is the most common IFI. Aspergillus nidulans infections seem to display a unique interaction with the CGD host and are seldom reported in other immunocompromised hosts. The occurrence of mucormycosis in the CGD host is mainly noted in the setting of treatment of inflammatory complications with immunosuppressive drugs. Candida infections are infrequently seen and show an age-dependent clinical presentation mainly affecting infants and young children. Furthermore, the child with CGD is susceptible to a wide range of fungal pathogens, indicating the need to determine the causative fungus, often by invasive diagnostic approaches, to guide optimal and rational treatment. Currently, it is becoming more and more clear that the exaggerated inflammatory response to fungal infection in the CGD host is leading in the pathogenesis, and antiinflammatory treatment might become as important as antifungal treatment in this specific host.     

Breakthrough Invasive Fungal Infections in Patients with Acute Myeloid Leukemia

Mycopathologia - We sought to determine the occurrence, risk factors, effect of antifungal prophylaxis, and outcomes of invasive fungal infections (IFIs) in patients with acute myeloid leukemia...     

Epidemiology of Invasive Fungal Infections in Patients with Acquired Immunodeficiency Syndrome at a Reference Hospital for Infectious Diseases in Brazil

Invasive fungal infections (IFIs) represent one of the main causes of morbimortality in immunocompromised patients. Pneumocystosis, cryptococcosis and histoplasmosis are the most frequently occurring IFIs in patients with acquired immunodeficiency syndrome (AIDS). Fungi, such as Candida spp. and Aspergillus spp., may cause severe diseases during the course of an HIV infection. Following the introduction of highly active anti-retroviral therapy, there has been a marked reduction of opportunistic fungal infections, which today is 20–25 % of the number of infections observed in the mid-1990s. This study is an observational and retrospective study aimed at the characterising IFI incidence and describing the epidemiology, clinical diagnostic and therapeutic features and denouement in HIV/AIDS patients. In HIV/AIDS patients, the IFI incidence is 54.3/1,000 hospitalisation/year, with a lethality of 37.7 %. Cryptococcosis represents the main opportunistic IFI in the population, followed by histoplasmosis. Nosocomial pathogenic yeast infections are caused principally by Candida spp., with a higher candidemia incidence at our institution compared to other Brazilian centres.     

(1,3)-β-D-葡聚糖在诊断深部真菌感染中的意义

探讨(1,3)-β-D-葡聚糖(BG)检测对于诊断深部真菌感染的临床意义。收集2009年同时进行(1,3)-β-D-葡聚糖检测和真菌培养的住院患者的临床资料。分析不同科室送检真菌抗原情况,重症医学科的(1,3)-β-D-葡聚糖检测阳性者真菌菌种分布情况以及(1,3)-β-D-葡聚糖检测假阳性情况。同时送检(1,3)-β-D-葡聚糖和真菌培养共275例,重症医学科送检最多,共178例:重症医学科(1,3)-β-D-葡聚糖检测阳性36例(阳性率20.22%);重症医学科(1,3)-β-D-葡聚糖检测阳性同时真菌培养阳性者25例,其中白假丝酵母菌10例,热带假丝酵母菌7例,光滑假丝酵母菌4例,阿萨希毛孢子菌2例,克柔假丝酵母菌1例,烟曲霉1例。11例(1,3)-β-D-葡聚糖假阳性,9例存在细菌菌血症。重症医学科等科室应加强真菌感染监测。深部真菌感染中,假丝酵母菌属感染最多见。细菌菌血症可能造成(1,3)-β-D-葡聚糖检测假阳性。     

Epidemiologic Research of Invasive Fungal Infections Using Large Healthcare Databases

Current Fungal Infection Reports - Invasive fungal infections (IFI) have become an important cause of morbidity and mortality over the past several decades, especially among immunocompromised...     

Epidemiology of Candidemia in Latin America: A Laboratory-Based Survey

Background

The epidemiology of candidemia varies depending on the geographic region. Little is known about the epidemiology of candidemia in Latin America.

Methods

We conducted a 24-month laboratory-based survey of candidemia in 20 centers of seven Latin American countries. Incidence rates were calculated and the epidemiology of candidemia was characterized.

Results

Among 672 episodes of candidemia, 297 (44.2%) occurred in children (23.7% younger than 1 year), 36.2% in adults between 19 and 60 years old and 19.6% in elderly patients. The overall incidence was 1.18 cases per 1,000 admissions, and varied across countries, with the highest incidence in Colombia and the lowest in Chile. Candida albicans (37.6%), C. parapsilosis (26.5%) and C. tropicalis (17.6%) were the leading agents, with great variability in species distribution in the different countries. Most isolates were highly susceptible to fluconazole, voriconazole, amphotericin B and anidulafungin. Fluconazole was the most frequent agent used as primary treatment (65.8%), and the overall 30-day survival was 59.3%.

Conclusions

This first large epidemiologic study of candidemia in Latin America showed a high incidence of candidemia, high percentage of children, typical species distribution, with C. albicans, C. parapsilosis and C. tropicalis accounting for the majority of episodes, and low resistance rates.     

Aerosolized Antifungals for the Prevention and Treatment of Invasive Fungal Infections

Invasive fungal infections result in significant morbidity and mortality, most notably in immunosuppressed patients. Aerosolized antifungal agents have been utilized primarily as prophylaxis (either alone or in combination with systemic antifungals) in patients at highest risk of invasive infections in attempts to optimize drug delivery while minimizing the potential for systemic toxicity and/or drug interactions. Published clinical experience with aerosolized antifungals most frequently involves various formulations of the polyene amphotericin B in patients undergoing lung transplantation and/or select patients with hematologic malignancy. Adverse events are infrequent and generally limited to dyspnea, dysgeusia, and cough. Existing data suggests lipid-based amphotericin B formulations may be better tolerated than amphotericin B deoxycholate. Published clinical experience with aerosolized antifungals as adjunctive treatment of invasive fungal infections is limited to case reports. Currently, there is insufficient evidence to support use of aerosolized echinocandins and azoles in clinical practice. Outstanding questions regarding comparative efficacy, optimal dose, duration and drug delivery present a continuing challenge when utilizing these agents in clinical practice.     

Malassezia Species: A Rare Cause of Invasive Fungal Infections in Immunocompromised Patients

The members of Malassezia species, which may cause skin disorders in healthy individuals, are associated with both cutaneous and systemic disorders in immunocompromised patients. These disorders include folliculitis, seborrheic dermatitis, catheter-related fungemia, and deeply invasive infections. This review examines not only the risk factors and pathogenesis of this rare fungal infection but also the clinical manifestations, diagnosis, and treatment of Malassezia infections in immunocompromised patients. Reports from several series of immunocompromised patients have shown low mortality rates with appropriate treatment.     

Advancing the Field: Evidence for New Management Strategies in Invasive Fungal Infections

Invasive fungal infections (IFI) are a significant cause of morbidity and mortality in the immunocompromised. The traditional diagnostic methods of culture and histological examination lack sensitivity and often only make a diagnosis late when the fungal burden is high, reducing the chances of cure even with the availability of new more potent and less toxic antifungal agents. New non-culture-based serological and PCR assays have been developed. These appear more sensitive and are able to make an earlier diagnosis as compared with traditional diagnostic methods. Early diagnosis is central to reducing IFI-related morbidity and mortality. This review describes the diagnostic potential of the new serological and PCR assays and outlines how these assays have been incorporated into algorithms to improve the management of IFI.     

Risk Factors and Outcomes of Invasive Fungal Infections in Allogeneic Hematopoietic Cell Transplant Recipients

Allogeneic hematopoietic cell transplant (HCT) recipients are at increased risk of invasive fungal infections (IFI), which are associated with a high mortality rate. We evaluated the impact of IFI in allogeneic HCT patients. In total, 541 consecutive allogeneic HCT recipients were included. The cumulative incidence of any IFI and mold infections at 1-year post-HCT was 10 and 7%, respectively. Median times to IFI and mold infection were 200 and 210 days, respectively. There was a trend toward fewer IFI and mold infections in the last several years. Both acute graft-versus-host disease (GVHD) (OR 1.83, p = 0.05) and corticosteroid duration (OR 1.0, p = 0.026) were significantly associated with increased risk of IFI, acute GVHD (OR 2.3, p = 0.027) emerged as the most important association with mold infections. Any IFI [HR 4.1 (2.79–6.07), p < 0.0001] and mold infections [HR 3.34 (2.1–5.1), p < 0.0001] were independently associated with non-relapse mortality (NRM). This association persisted in the setting of both acute and chronic GVHD. Corticosteroid treatment for >90 days was also significantly associated with higher NRM [HR 1.9 (1.3–2.6), p < 0.0001]. This study highlights the impact of IFI on NRM among HCT patients. The decrease in number of IFI and mold infections over the last several years may reflect the benefit of prophylaxis with mold-active antifungal agents.